[go: up one dir, main page]

WO1995018109A1 - Nouveaux derives antiviraux de 2,4-pyrimidinedione et leurs procedes de preparation - Google Patents

Nouveaux derives antiviraux de 2,4-pyrimidinedione et leurs procedes de preparation Download PDF

Info

Publication number
WO1995018109A1
WO1995018109A1 PCT/KR1994/000178 KR9400178W WO9518109A1 WO 1995018109 A1 WO1995018109 A1 WO 1995018109A1 KR 9400178 W KR9400178 W KR 9400178W WO 9518109 A1 WO9518109 A1 WO 9518109A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
pyrimidinedione
compound
optionally substituted
ethyl
Prior art date
Application number
PCT/KR1994/000178
Other languages
English (en)
Inventor
Jong Chan Son
Ill Young Lee
Byung Il Bae
Jeong Sik Han
Joong Kwon Choi
Yung Bok Chae
Original Assignee
Korea Research Institute Of Chemical Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR2019930028908U external-priority patent/KR0132614Y1/ko
Priority claimed from KR2019930028909U external-priority patent/KR950017498U/ko
Application filed by Korea Research Institute Of Chemical Technology filed Critical Korea Research Institute Of Chemical Technology
Priority to JP7517935A priority Critical patent/JP2935573B2/ja
Priority to EP95903455A priority patent/EP0736015B1/fr
Priority to DE69426836T priority patent/DE69426836D1/de
Priority to US08/656,354 priority patent/US5747500A/en
Priority to AU12502/95A priority patent/AU1250295A/en
Priority to AT95903455T priority patent/ATE199549T1/de
Publication of WO1995018109A1 publication Critical patent/WO1995018109A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms

Definitions

  • the present inventors have studied for a long time in search for 2,4-pyrimidinedione compounds which have a strong activity against HIV as well as a lower toxicity, and, as a result, have discovered that 2,4-pyrimidinedione compounds with an allyl or propargyl group in the N-1 position of the 2,4-pyrimidinedione ring exhibit strong antiviral activities against HIV.
  • R 3 and R 4 represent independently a hydrogen or halogen atom, or a hydroxy, C 1-3 alkyl, fluoromethyl, C 1-3 alkoxy, amino,
  • R 2 , R 3 and R 4 have the same meanings as defined previously.
  • step (c) the compound (VI) is reacted with an arylthio compound, e.g., 3,5-dimethylthiophenol, in an alcoholic solvent, e.g., ethanol, in the presence of a base, e.g., potassium hydroxide, to provide a compound of formula (II-a) (step (c)).
  • an arylthio compound e.g., 3,5-dimethylthiophenol
  • an alcoholic solvent e.g., ethanol
  • a base e.g., potassium hydroxide
  • step (d) the compound of formula (VII) obtained in step (d) above is reacted with a base, e.g., sodium hydride, in a polar solvent, e.g., dimethylformamide, under an oxygen containing atmosphere to provide a compound of formula (VIII) (step (f)), which is hydrolyzed by the method described in the step (b) above to provide a compound of formula (II-c) (step (g)).
  • a base e.g., sodium hydride
  • a polar solvent e.g., dimethylformamide
  • step (j) the compound (X) is subjected to a hydrogen addition reaction in an alcoholic solvent, e.g., ethanol in the presence of a palladium catalyst, e.g., 10% palladium-on-carbon, to provide a compound of formula (Il-d) (step (j)).
  • an alcoholic solvent e.g., ethanol
  • a palladium catalyst e.g., 10% palladium-on-carbon
  • any one of R 1 , R 3 and R 4 in formula (I) is an amino group
  • inorganic acid salts as a hydrochloride, hydrobromide, sulfate, phosphate, nitrate, perchlorate and the like
  • organic carboxylic and sulfonic acid salts as a formate, acetate, propionate, succinate, glycolate, lactate, fumarate, 4-hydroxybenzoate, methanesulfonate, ethanesulf ⁇ nate and the like are also included within the scope of the pharmaceutically acceptable salts of the present invention.
  • the 2,4-pyrimidinedione compounds (I) of the present invention and their pharmaceutically acceptable salts possess a strong antiviral activity, particularly against HIV.
  • the present invention also includes within its scope pharmaceutical compositions comprising one or more of the compounds(I) and their above-mentioned salts as active ingredients, in association with pharmaceutically acceptable carriers, excipients or other additives, if necessary.
  • compositions of the invention may be formulated for administration orally .or by injection.
  • the composition for oral administration may take various forms such as tablets and gelatin capsules, which may contain conventional additives such as a diluent (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine), a lubricant (e.g., silica, talc, stearic acid or its magnesium and calcium salts and polyethylene glycol).
  • a diluent e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine
  • a lubricant e.g., silica, talc, stearic acid or its magnesium and calcium salts and polyethylene glycol.
  • the composition may further comprise a coupling agent (e.g., magnesium aluminum silicate, starch paste, gelatin, tragakans, methyl cellulose, sodium carboxymethyl cellulose and polyvinyl picolidine) and optionally a dusting agent (e.g., starch, agar and alginic acid or its sodium salt), absorbent, colorant, favour, sweetener and the like.
  • a coupling agent e.g., magnesium aluminum silicate, starch paste, gelatin, tragakans, methyl cellulose, sodium carboxymethyl cellulose and polyvinyl picolidine
  • a dusting agent e.g., starch, agar and alginic acid or its sodium salt
  • the pharmaceutical compositions can be prepared by a conventional mixing, granulating or coating method and may comprise preferably about 0.1 to 75 %, more preferably about 1 to 50 % of an active ingredient.
  • the unit dosage of the composition suitable for the administration to human of a weight of about 50 to 70 kg may comprise about 10 to 200mg of the active ingredient.
  • the evaporation was conducted under a reduced pressure, preferably under a pressure ranging from about 15 to 100 mmHg, and the flash chromatography was carried out by using Merck Kieselgel 60, 230-400 mesh marketed by Merck.
  • Step 2 Synthesis of 5-ethyl-6-(3,5-dimethylbenzoyl)-2,4- pyrimidinedione
  • HCl-methanol (1:2) was refluxed with stirring for about 16 hours and evaporated under reduced pressure to give a light yellow residue, which was recrystallized from methanol-chloroform (5:1) to afford 480 mg (yield 88 %) of the title compound as a white solid.
  • Example 1 Synthesis of 1-propargyl-5-ethyl-6-phenylthio-2,4- pyrimidinedione To a stirred solution of 248 mg (1 mmol) of the compound obtained from Preparation 1 and 138 mg (1 mmol) of anhydrous potassium carbonate in 5 ml of DMF was added 130 ⁇ l (1.2 mmol) of propargyl bromide. The reation mixture was stirred for about 24 hours at room temperature and evaporated under reduced pressure to give a yellow residue, which was purified by flash chromatography using a mixture of ethyl acetate and hexane (1:2) as an eluent to afford 120 mg (yield 42 %) of the title compound as a white solid.
  • Example 5 Synthesis of 1-(trans-2-butenyl)-5-ethyl-6-(3,5- dimethylbenzyl)-2,4-pyrimidinedione To a stirred solution of 258 mg (1 mmol) of the compound obtained from Preparation 5 in 5 ml of DMF were added 138 mg (1 mmol) of anhydrous potassium carbonate and 121 ⁇ l (1 mmol) of 85% trans-crotyl bromide at room temperature.
  • Example 8 Synthesis of 1-(methoxycarbonylallyl)-5-ethyl-6- (3,5-dimethylbenzoyl)-2,4-pyrimidinedione To a stirred solution of 272 mg (1 mmol) of the compound obtained from Preparation 6 and 138 mg (1 mmol) of anhydrous potassium carbonate in 5 ml of DMF was added 138 ⁇ l (1 mmol) of 85% methyl 4-bromocrotonate at room temperature.
  • Example 74 Synthesis of 1- ( 4-azido-trans-2-butenyl ) -5-isopropyl-6- ( 3 , 5-dimethylbenzoyl ) -2 , 4-pyrimidinedione To a stirred solution of 187 mg (0.5 mmol) of the compound obtained from Example 9 in 5 ml of DMF was added 98 mg (1.5 mmol) of sodium azide at room temperature.
  • Example 75 Synthesis of 1-(4-acetoxy-trans-2-butenyl)-5- isopropyl-6-(3,5-dimethylbenzoyl)-2,4- pyrimidinedione To a solution of 187 mg (0.5 mmol) of the compound obtained from Example 9 in 5 ml of DMF was added 410 mg (5 mmol) of sodium acetate. The reaction mixture was then stirred for about 48 hours at 100 °C, and evaporated under reduced pressure to give a yellow-colored residue, which was purified by flash chromatography using a mixture of ethyl acetate and hexane (1:2) as an eluent to afford 140 mg (yield 70 %) of the title compound as a colorless syrup.
  • Example 79 Synthesis of 1-(4-azido-trans-2-butenyl)-5-ethyl- 6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione To a stirred solution of 200 mg (0.55 mmol) of the compound obtained from Example 47 in 5 ml of DMF was added 108 mg (1.66 mmol) of sodium azide at room temperature.
  • Example 80 Synthesis of 1-(4-acetoxy-trans-2-butenyl)-5- ethyl-6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione
  • the anti-HIV assays were based on the inhibition of the virus-induced cytopathic effect in MT-4 cells as described in J. Virol. Methods, 16, 171 (1987). Briefly, MT-4 cells were suspended in culture medium at 2.5 ⁇ 10 5 cells/ml and infected with 1000 CCID 50 (50% cell culture infective dose) of HIV. Immediately, after virus infection, 100 ⁇ l of the cell suspension was brought into each well of a flat-bottomed microtiter tray containing various concentrations of the test compounds.
  • the number of viable cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, as disclosed in J. Virol. Methods, 20, 309 (1988).
  • MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
  • the cytotoxicity of the compounds of the present invention was assessed in parallel with their antiviral activity. It was based on the viability of mock-infected host cells as determined by the MTT methods (see J. Virol. Methods, 20 , 309 (1988)).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Nouveaux composés de 2,4-pyrimidinedione, et leurs sels pharmaceutiquement acceptables présentant de bonnes activités antivirales, répondant à la formule (I), dans laquelle R1 représente un groupe allyle éventuellement substitué représenté par CH¿2?CH=CR?5R6¿, ou un groupe propargyle éventuellement substitué représenté par CH¿2?C CR?7, où R5, R6 et R7¿, indépendamment les uns des autres, représentent un atome d'hydrogène; un groupe méthyle éventuellement substitué par un atome d'halogène, ou un radical carbonyloxy C¿1-10?, hydroxy, azido, cyano, amino éventuellement substitué, phosphonyle éventuellement substitué, phényle éventuellement substitué, hétéroaryle C3-10, alcoxy C1-3 ou benzyloxy; un groupe alcényle ou alkyle C2-10; un groupe cyclopropyle; un groupe phényle éventuellement substitué; un groupe hétéroaryle C3-10; un groupe ester C1-10; ou un groupe alkylamide C1-10 éventuellement substitué; R?2¿ représente un atome d'halogène, un groupe alkyle C¿1-5?, cycloalkyle C3-6, alcényle C2-8 ou alcynyle C2-8 éventuellement substitué, ou un groupe benzyle; R?3 et R4¿, indépendamment l'un de l'autre, représentent un atome d'hydrogène ou d'halogène, ou un groupe hydroxy, alkyle C¿1-3?, fluorométhyle, alcoxy C1-3, amino, alkylester C2-6 ou alkylamide C2-7; A représente un atome d'oxygène ou de soufre; Z représente un atome d'oxygène ou de soufre; un groupe carbonyle; un groupe amino; ou un groupe méthylène éventuellement substitué par au moins un élément sélectionné dans le groupe constitué d'un atome d'halogène et de groupes cyano, hydroxy, azido, amino, alkylamide C1-3, ester C1-4 et nitro.
PCT/KR1994/000178 1993-12-21 1994-12-20 Nouveaux derives antiviraux de 2,4-pyrimidinedione et leurs procedes de preparation WO1995018109A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP7517935A JP2935573B2 (ja) 1993-12-21 1994-12-20 新規な抗ウイルス性２，４−ピリミジンジオン誘導体及びその製造方法
EP95903455A EP0736015B1 (fr) 1993-12-21 1994-12-20 Derives antiviraux de 2,4-pyrimidinedione et leurs procedes de preparation
DE69426836T DE69426836D1 (de) 1993-12-21 1994-12-20 Antivirale 2,4-pyrimidindion-derivate und verfahren zu ihrer herstellung
US08/656,354 US5747500A (en) 1993-12-21 1994-12-20 Antiviral 2, 4-pyrimidinedione derivatives
AU12502/95A AU1250295A (en) 1993-12-21 1994-12-20 Novel antiviral 2,4-pyrimidinedione derivatives and processes for the preparation thereof
AT95903455T ATE199549T1 (de) 1993-12-21 1994-12-20 Antivirale 2,4-pyrimidindion-derivate und verfahren zu ihrer herstellung

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
KR1993/28909 1993-12-21
KR2019930028908U KR0132614Y1 (ko) 1993-12-21 1993-12-21 자동차의 좌석 틸트장치
KR2019930028909U KR950017498U (ko) 1993-12-21 1993-12-21 자동차의 스태빌라이저 장착구조
KR1993/28908 1993-12-21
KR1994/10264 1994-05-11
KR1994/10262 1994-05-11
KR1994/10263 1994-05-11
KR19940010264 1994-05-11
KR19940010262 1994-05-11
KR19940010263 1994-05-11
KR1994/29388 1994-11-10
KR1019940029388A KR0151811B1 (ko) 1993-12-21 1994-11-10 신규한 항바이러스성 2,4-피리미딘디온 유도체 및 그의 제조방법

Publications (1)

Publication Number Publication Date
WO1995018109A1 true WO1995018109A1 (fr) 1995-07-06

Family

ID=27555064

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR1994/000178 WO1995018109A1 (fr) 1993-12-21 1994-12-20 Nouveaux derives antiviraux de 2,4-pyrimidinedione et leurs procedes de preparation

Country Status (8)

Country Link
US (1) US5747500A (fr)
EP (1) EP0736015B1 (fr)
JP (1) JP2935573B2 (fr)
KR (1) KR0151811B1 (fr)
AT (1) ATE199549T1 (fr)
AU (1) AU1250295A (fr)
DE (1) DE69426836D1 (fr)
WO (1) WO1995018109A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997030979A1 (fr) * 1996-02-22 1997-08-28 Samjin Pharmaceutical Co., Ltd. Nouveaux derives nucleosidiques homocarbocycliques de pyrimidinedione substituee, leurs procedes de preparation, et compositions les renfermant a titre d'ingredients actifs
EP1035116A1 (fr) * 1999-03-10 2000-09-13 Samjin Pharmaceutical Co., Ltd. Procédé de préparation de la 1-[(cyclopent-3-en-1-yl)-methyl]-5-ethyl-6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione
WO2000061564A1 (fr) * 1999-04-10 2000-10-19 Samjin Pharmaceutical Co., Ltd. Derives de pyrimidinedione, a propriete antivirale, et procede de preparation associe
EP1159271A4 (fr) * 1999-03-04 2002-06-05 Korea Res Inst Chem Tech Derives de 2,4-pyrimidinedione antiviraux et leur procede de preparation
EP0912526B1 (fr) * 1996-05-16 2003-03-05 Korea Research Institute of Chemical Technology Derives 2,4-pyrimidinedione antiviraux et procede de fabrication associe
US6545007B2 (en) 2000-11-17 2003-04-08 Idenix (Cayman) Limited Methods for inhibiting the transmission of HIV using topically applied substituted 6-benzyl-4-oxopyrimidines
WO2009005674A3 (fr) * 2007-06-29 2009-09-24 Gilead Sciences, Inc. Nouveaux inhibiteurs de la transcriptase inverse du vih
US8835449B2 (en) 2011-11-11 2014-09-16 Pfizer Inc. 2-thiopyrimidinones
US9771332B2 (en) 2015-05-05 2017-09-26 Pfizer Inc. 2-thiopyrimidinones

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5476855A (en) * 1993-11-02 1995-12-19 Mahmoud H. el Kouni Enzyme inhibitors, their synthesis and methods for use
EP0967208B1 (fr) * 1998-06-26 2002-08-14 Crompton Vinyl Additives GmbH 6-aminouracils substitués en position 5 comme stabilisants pour des polymères halogenes
IT1305313B1 (it) * 1998-07-17 2001-05-04 Colla Paolo 3,4 - diidro- 6- benzil-4-oxopirimidine sostituite e relativo processodi produzione e impiego nella terapia delle infezioni da hiv-1.
KR100368891B1 (ko) * 1999-03-04 2003-01-24 한국화학연구원 신규한 항바이러스성 2,4-피리미딘디온 유도체
KR20020074683A (ko) * 2001-03-21 2002-10-04 주식회사 엘지씨아이 항바이러스성 2,4-피리미딘디온 유도체 및 그의 제조방법
KR101257378B1 (ko) * 2006-04-19 2013-04-23 삼진제약주식회사 항바이러스성 피리미딘디온 유도체 및 이의 제조 방법
US8354421B2 (en) * 2007-06-29 2013-01-15 Korea Research Insitute Of Chemical Technology HIV reverse transcriptase inhibitors
KR20100092960A (ko) * 2007-12-21 2010-08-23 한국화학연구원 Ｈｉｖ 역전사 효소 억제제의 제조 방법

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4730001A (en) * 1986-01-22 1988-03-08 Southern Research Institute Carbocyclic analogues of amino and azido thymidines
EP0420763A2 (fr) * 1989-09-29 1991-04-03 Mitsubishi Chemical Corporation Dérivés de nucléosides d'acyclopyrimidines 6-substituées et agent antiviral les contenant comme ingrédients actifs
EP0484843A1 (fr) * 1990-11-05 1992-05-13 E.R. SQUIBB & SONS, INC. Une cyclobutyl pyrimidine optiquement active
US5318972A (en) * 1990-03-29 1994-06-07 Mitsubishi Kasei Corporation Pyrimidine nucleoside derivative and antiviral agent containing the derivative as active ingredient

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0442473B1 (fr) * 1990-02-15 1998-08-19 Takeda Chemical Industries, Ltd. Dérivés de la pyrimidinedione, leur préparation et leur utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4730001A (en) * 1986-01-22 1988-03-08 Southern Research Institute Carbocyclic analogues of amino and azido thymidines
EP0420763A2 (fr) * 1989-09-29 1991-04-03 Mitsubishi Chemical Corporation Dérivés de nucléosides d'acyclopyrimidines 6-substituées et agent antiviral les contenant comme ingrédients actifs
US5318972A (en) * 1990-03-29 1994-06-07 Mitsubishi Kasei Corporation Pyrimidine nucleoside derivative and antiviral agent containing the derivative as active ingredient
EP0484843A1 (fr) * 1990-11-05 1992-05-13 E.R. SQUIBB & SONS, INC. Une cyclobutyl pyrimidine optiquement active

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1092647C (zh) * 1996-02-22 2002-10-16 三进制药株式会社 新抗病毒的取代嘧啶二酮同素碳环核苷衍生物及其制备方法与含有其为活性成分的组合物
US5922727A (en) * 1996-02-22 1999-07-13 Samjin Pharmaceutical Co., Ltd Antiviral substituted pyrimidinedione homocarbocyclic nucleoside derivatives and methods for the preparation thereof and compositions containing the same as active ingredients
JP3049095B2 (ja) 1996-02-22 2000-06-05 サムジン ファーマシューチカル カンパニー，リミテッド 新規抗ウイルス性置換ピリミジンジオン単素炭素環式ヌクレオシド誘導体及びその製造方法とこれを活性成分として含有する組成物
WO1997030979A1 (fr) * 1996-02-22 1997-08-28 Samjin Pharmaceutical Co., Ltd. Nouveaux derives nucleosidiques homocarbocycliques de pyrimidinedione substituee, leurs procedes de preparation, et compositions les renfermant a titre d'ingredients actifs
EP0912526B1 (fr) * 1996-05-16 2003-03-05 Korea Research Institute of Chemical Technology Derives 2,4-pyrimidinedione antiviraux et procede de fabrication associe
EP1159271A4 (fr) * 1999-03-04 2002-06-05 Korea Res Inst Chem Tech Derives de 2,4-pyrimidinedione antiviraux et leur procede de preparation
EP1035116A1 (fr) * 1999-03-10 2000-09-13 Samjin Pharmaceutical Co., Ltd. Procédé de préparation de la 1-[(cyclopent-3-en-1-yl)-methyl]-5-ethyl-6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione
RU2203891C2 (ru) * 1999-04-10 2003-05-10 Самдзин Фармасьютикал Ко., Лтд. Антивирусные производные пиримидиндиона, способ их получения и фармацевтическая композиция на их основе
WO2000061563A1 (fr) * 1999-04-10 2000-10-19 Samjin Pharmaceutical Co., Ltd. Derives de pyrimidinedione antiviraux et procede de preparation de ceux-ci
WO2000061564A1 (fr) * 1999-04-10 2000-10-19 Samjin Pharmaceutical Co., Ltd. Derives de pyrimidinedione, a propriete antivirale, et procede de preparation associe
AU760332B2 (en) * 1999-04-10 2003-05-15 Samjin Pharmaceutical Co., Ltd. Antiviral pyrimidinedione derivatives and process for the preparation thereof
US6987114B1 (en) 1999-04-10 2006-01-17 Samjin Pharmaceutical Co., Ltd Antiviral pyrimidinedione derivatives and process for the preparation thereof
US6545007B2 (en) 2000-11-17 2003-04-08 Idenix (Cayman) Limited Methods for inhibiting the transmission of HIV using topically applied substituted 6-benzyl-4-oxopyrimidines
WO2009005674A3 (fr) * 2007-06-29 2009-09-24 Gilead Sciences, Inc. Nouveaux inhibiteurs de la transcriptase inverse du vih
CN101784532A (zh) * 2007-06-29 2010-07-21 韩国化学研究院 新的hiv逆转录酶抑制剂
US8835449B2 (en) 2011-11-11 2014-09-16 Pfizer Inc. 2-thiopyrimidinones
US8841314B2 (en) 2011-11-11 2014-09-23 Pfizer Inc. 2-Thiopyrimidinones
US9399626B2 (en) 2011-11-11 2016-07-26 Pfizer Inc. 2-thiopyrimidinones
US9873673B2 (en) 2011-11-11 2018-01-23 Pfizer Inc. 2-thiopyrimidinones
US9771332B2 (en) 2015-05-05 2017-09-26 Pfizer Inc. 2-thiopyrimidinones

Also Published As

Publication number Publication date
KR0151811B1 (ko) 1998-10-15
EP0736015A1 (fr) 1996-10-09
JP2935573B2 (ja) 1999-08-16
KR950017971A (ko) 1995-07-22
AU1250295A (en) 1995-07-17
EP0736015B1 (fr) 2001-03-07
JPH09509405A (ja) 1997-09-22
DE69426836D1 (de) 2001-04-12
ATE199549T1 (de) 2001-03-15
US5747500A (en) 1998-05-05

Similar Documents

Publication Publication Date Title
EP0736015B1 (fr) Derives antiviraux de 2,4-pyrimidinedione et leurs procedes de preparation
RU2102393C1 (ru) (-)-цис-4-амино-1-(2-оксиметил-1,3-оксатиолан-5-ил-(1н)-пиримидин-2-он в кристаллических формах, способы их получения и фармацевтическая композиция
US5719154A (en) Oxazolidinone antibacterial agents having a six-membrane heteroaromatic ring
EP0420763B1 (fr) Dérivés de nucléosides d'acyclopyrimidines 6-substituées et agent antiviral les contenant comme ingrédients actifs
EP0371139B1 (fr) Derives de nucleoside de pyrimidine acyclique substitue en 6 et agents antiviraux contenant ces composes en tant qu'ingredients actifs
US5461060A (en) Pyrimidine derivatives and anti-viral agent containing the same as active ingredient thereof
EP0912526B1 (fr) Derives 2,4-pyrimidinedione antiviraux et procede de fabrication associe
EP1159271B1 (fr) Derives de 2,4-pyrimidinedione antiviraux et leur procede de preparation
US5318972A (en) Pyrimidine nucleoside derivative and antiviral agent containing the derivative as active ingredient
EP1100786B1 (fr) Derives de pyrimidinedione, a propriete antivirale, et procede de preparation associe
RU2481341C2 (ru) Кристаллические модификации 3-(1н-индол-3-ил)-4-[2-(4-метилпиперазин-1-ил)хиназолин-4-ил]пиррол-2,5-диона
US4587254A (en) 1,3,4-thiadiazole derivatives, process for the production thereof and use thereof as antiulcer agent
US4495192A (en) 1-Substituted 1,4-dihydropyridines
US20010020022A1 (en) 2{3-[4-(2-t-butyl-6-trifluoromethylpyridin-4-yl) piperazin-1-yl] propylmercapto} pyrimidin-4-ol-fumarate
HU205745B (en) Process for producing new imidazolidine derivatives and pharmaceutical compositions comprising same
US4203980A (en) Benzylpyrimidine derivatives
EP0098942B1 (fr) Composés d'imidazolylpropanol optiquement activés et leur fabrication et utilisation
EP0682023B1 (fr) Dérivés d'imidazopyridine et procédé pour leur préparation
USRE37979E1 (en) Pyrimidine derivatives and anti-viral agent containing the same as active ingredient thereof
KR0180581B1 (ko) 신규한 항바이러스성 1-알킬-2,4-피리미딘디온 유도체 및 그의 제조방법
US5753672A (en) Imidazopyridine derivatives and process for preparing the same
KR100220605B1 (ko) N-1 위치가 알콕시카르보닐메틸렌기 또는 아릴옥시카르보닐메틸렌기로 치환된 신규한 항바이러스성 2,4-피리미딘디온 유도체 및 그의 제조방법
JPH03284624A (ja) 抗ウイルス剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 08656354

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 1995903455

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1995903455

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: CA

WWG Wipo information: grant in national office

Ref document number: 1995903455

Country of ref document: EP